ViRPET - COMBINATION OF VIRTUAL REALITY AND PET BRAIN IMAGING

ABSTRACT

Various methods, systems and apparatus are provided for brain imaging during virtual reality stimulation. In one example, among others, a system for virtual ambulatory environment brain imaging includes a mobile brain imager configured to obtain positron emission tomography (PET) scans of a subject in motion, and a virtual reality (VR) system configured to provide one or more stimuli to the subject during the PET scans. In another example, a method for virtual ambulatory environment brain imaging includes providing stimulation to a subject through a virtual reality (VR) system; and obtaining a positron emission tomography (PET) scan of the subject while moving in response to the stimulation from the VR system. The mobile brain imager can be positioned on the subject with an array of imaging photodetector modules distributed about the head of the subject.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority to, and the benefit of, co-pending U.S.provisional application entitled “ViRPET—Combination of Virtual Realityand PET Brain Imaging” having Ser. No. 62/091,790, filed Dec. 15, 2014,which is hereby incorporated by reference in its entirety.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

This invention was made with government support under agreementDE-AC05-06OR23177 awarded by the Department of Energy. The Governmenthas certain rights in the invention.

BACKGROUND

Positron emission tomography (PET) is a well-established molecularimaging modality. Current clinical PET scanners are large, bulky devicesthat are placed in dedicated imaging rooms and require the subject to bebrought to the imager. With very few exceptions, PET scanners aretypically limited to imaging subjects in a supine or prone position.They are also typically combined with CT scanners, which are not easilyamenable to other than horizontal imaging geometries. Functionalmagnetic resonance imaging (fMRI) cannot be used for functional brainimaging of upright subjects, because present day upright MRI scanners donot provide strong enough magnetic field for functional imaging. Inaddition, MRI requires that the subject be immobile during the scan.

BRIEF DESCRIPTION OF THE DRAWINGS

Many aspects of the present disclosure can be better understood withreference to the following drawings. The components in the drawings arenot necessarily to scale, emphasis instead being placed upon clearlyillustrating the principles of the present disclosure. Moreover, in thedrawings, like reference numerals designate corresponding partsthroughout the several views.

FIGS. 1A through 1F are examples of mobile brain imagers of a virtualambulatory environment brain imaging system in accordance with variousembodiments of the present disclosure.

FIGS. 2A and 2C are examples of imaging photodetector modules of amobile brain imager of FIGS. 1A-1F in accordance with variousembodiments of the present disclosure.

FIGS. 2B and 2D illustrate characteristics of the imaging photodetectormodules of FIGS. 2A and 2C in accordance with various embodiments of thepresent disclosure.

FIGS. 3A through 3C are examples of support systems for the mobile brainimagers of FIGS. 1A-1F in accordance with various embodiments of thepresent disclosure.

FIGS. 4A and 4B are examples of visual interfaces for a virtual realitysystem of the virtual ambulatory environment brain imaging system inaccordance with various embodiments of the present disclosure.

FIGS. 5A through 5C illustrate an example of a mobility platform for thevirtual reality system of the virtual ambulatory environment brainimaging system in accordance with various embodiments of the presentdisclosure.

FIG. 6 shows a series of multi-slice reconstructed images of amulti-compartmental Hoffman brain phantom obtained with the mobile brainimager of FIG. 3A in accordance with various embodiments of the presentdisclosure.

FIGS. 7A-7B, 8A-8B and 9A-9B show examples of brain images of a patientin accordance with various embodiments of the present disclosure.

DETAILED DESCRIPTION

Disclosed herein are various examples related to virtual ambulatoryenvironment brain imaging. The virtual ambulatory environment allowssubjects to be studied while in motion (e.g., walking, running, or otherbodily movements). The logistical and safety issues related to imagingthe brain of a moving subject can also be reduced by using the virtualambulatory environment. Reference will now be made in detail to thedescription of the embodiments as illustrated in the drawings, whereinlike reference numbers indicate like parts throughout the several views.

Many functional processes in the human brain depend on the subject'sposition and/or interaction with the surrounding environment. Examplesinclude imaging brains of patients who are undergoing post-stroke motorfunction impairment therapy while upright (standing) and/or exercising(e.g., on a treadmill, balancing platform, etc.). In addition, forpatients who cannot be still such as those with cognitive deficits(e.g., autism, Alzheimer's disease, schizophrenia) or those withphysical issues that prevent them from keeping still such as tremors,low dose imaging studies can provide insight into the brain functionrecovery and/or proscriptive personalized medicine/treatments plans inthese patients. Also, subjects who exhibit the so-called “savantsyndrome”, or those with behavioral expertise or abilities could beimaged while performing relevant tasks, and conversely, those withnegative behaviors such as PTSD or addition could be imaged in a moreimmersive environment, with either glucose or oxygen uptake or specifictargeted neurotransmitter receptor availability. Currently,electroencephalography (EEG), magnetoencephalography (MEG) ornear-infrared spectroscopy (NIRS) techniques can be used in theseindividuals when in the upright position, but these modalities do notprovide full coverage of the brain during activity. In addition, theseimaging modalities do not provide accurate high resolution molecularimages of the brain.

An ambulatory brain imaging system using a wearable mobile brain imagercan allow scanning and/or imaging to be carried out with the subject insupine, prone, or inclined positions, as well as in upright positionssuch as, e.g., sitting, standing, walking on treadmill, etc. Positronemission tomography (PET) is a high resolution functional brain imagingmodality that can be used in upright subjects who can move or turn theirheads. An ambulatory microdose PET (AMPET) imaging system can adapt towhole body movement of the subject. Combining PET withelectroencephalography (EEG) and near infrared spectroscopy (NIRS) canenhance the functional information gathered with the brain immersed inthe particular simulated environment. In fact, a combination of some orall of these modalities (e.g., PET/NIRS, PET/EEG, and/or PET/EEG/NIRS)can form the wearable mobile brain imager.

When used in conjunction with a virtual reality system, the impact ofstimuli from and/or interactions with the surrounding environment can beexamined. The virtual reality system can be implemented using videogoggles, display screens or other visual means such as mirrors,projection screens, etc. In one embodiment of the system, the imagercovers the eyes of the subject/patient to increase the sensitivity. Toprovide comfort to the subject/patient, as well as to deliver thestimulus of the VR environment, compact goggles with cameras for botheyes can be inserted between the detector and the eyes. A mobilityplatform can be used to allow the subjects or patients to be in motionor in various positions during the imaging. Position and/or movement ofthe subject or patient can be monitored to provide feedback to thevirtual reality system and/or the brain imager. The effect of a virtualambulatory environment on the functioning of the brain can be close tothe stimulation experienced by the human brain during real worldsituations, while eliminating logistical issues, controlling variables,and improving safety during imaging with the subject in motion. Inaddition, the virtual reality environment can be used to intensify theexternal stimuli on the brain by providing more intense environment forthe subject/patient to be immersed in with expected enhanced impact onthe functions of the brain. This can have for example importantimplications in virtual therapy.

How much the human brain will be tricked into believing that thesurrounding environment is “real” will depend on the quality of thevirtual reality environment (e.g., the visual and sound gear, thesoftware, speed of response, etc.) and also on the mobility platform. Toenhance the realistic impressions on the body and thus the brain, thesubject can be also subjected to physical stimuli such as, e.g., blowingand/or changing air flow (“wind”), temperature changes, painful stimuli,tactile stimuli, smells, and/or artificial rain or snow, in addition tothe visual and audio effects. Multiple physical sensory impacts canenhance the “realism” of the virtual ambulatory environment.

With reference to FIGS. 1A-1F, shown are examples of compact and mobilebrain imagers of brain imaging systems in accordance with variousembodiments of the present disclosure. The mobile brain imager 100 caninclude imaging photodetector modules 103 that are placed around andclose to the head of the subject or patient 106, or arranged as a set ofindividual imaging photodetector modules 103 surrounding the head of thesubject or patient 106 in an irregular tight pattern. For example, themobile brain imager 100 can include one or more rings (e.g., 1-4 rings)of imaging photodetector modules 103 for viewing the brain of a subjector patient 106. In FIG. 1A, the imaging photodetector modules 103 formtwo rings composed of 16 closely spaced and individually read imagingmodules 103. The rings of imaging photodetector modules 103 can providesurface coverage and angular views for high resolution 2D/3D PET imageslice reconstruction of the brain.

A semi-spherical geometry can improve the solid angle coverage, whichcan provide a higher sensitivity. In FIGS. 1B-1D, the imagingphotodetector modules 103 are positioned in groupings of tiles thattightly cover the head of the subject or patient 106. The imagingphotodetector modules 103 can be placed behind and/or above the head,and/or under the chin, to increase the detection efficiency especiallyin the central regions of the brain. The arrangement of the imagingphotodetector modules 103 is typically a tight fit to the head tomaximize sensitivity of the mobile brain imager 100. The imagingphotodetector modules 103 operate in a coincidence mode between allpairs in the set, as in a standard PET system. A light weight, but rigidsupport structure can support the imaging photodetector modules 103 in aprecise hemispherical arrangement.

FIGS. 1E and 1F illustrate a mobile brain imager 100 with imagingphotodetector modules 103 that extends over the eyes of thesubject/patient 106 to increase the sensitivity. Multiple rows ofphotodetector modules 103 (e.g., three as shown in FIG. 1E) can extenddownward from the crown of the head. To provide comfort to thesubject/patient 106, compact goggles 112 with cameras for both eyes canbe inserted between the photodetector modules 103 and the eyes of thesubject/patient 106.

The imaging photodetector modules 103 include a scintillator to producegamma rays and a coupled photodetector to detect the scintillation lightproduced by the absorbed gamma rays. The scintillator can comprisepixelated or plate crystal scintillator materials such as, e.g., LSO,LYSO, GSO, BGO, LaBr3, NaI(Tl), CsI(Tl), and/or CsI(Na). Thephotodetector can comprise, e.g., a standard or multi-elementphotomultiplier (PMT), avalanche photodiode (APD) arrays or large sizeAPD, and/or other silicon photomultipliers (SiPM). For example, fastscintillators such as LYSO and fast electronics can be used to exploitthe time of flight (TOF) characteristics of PET imaging. The TOFinformation improves the sensitivity and uniformity of response,especially in the “set of modules” variant with limited angularcoverage, and can reduce the artifacts in PET reconstruction images thatare caused by the incomplete angular sampling. High resolution TOF canprovide substantial remedy in addition to depth of interaction (DOI)information. A timing resolution of 100-350 psec full width at halfmaximum (FWHM) is useful in such a compact system, with sub-200 psectiming resolution being desirable.

The imaging photodetector modules 103 can be mounted in or on alightweight helmet 109 with an opening for the head and neck as in FIG.1B. The helmet 109 can include a ring or other arrangement of imagingphotodetector modules 103 attached to an inner shell or liner. Tomaximize the efficiency and minimize the injected doses, the imagingphotodetector modules 103 should be as close as possible to the head ofthe subject. A chin strap can be used to hold the assembly in positionon the head of the subject or patient 106. The attached imagingphotodetector modules 103 can be covered by an outer cover or shell,which can also encase other electronic circuitry associated with themobile brain imager 100. The outer cover can be configured toaccommodate a harness or tether to attach the assembly to an externalsupport mechanism for mechanical support. A head registration cap can beused to provide a kinematic registration to the head of the subject, inaddition to a comfortable fit for the helmet 109. The registration capmay be adjusted to accommodate the size and/or geometry of the head. Arigid and repeatable mount can be included on the registration cap toattach it to the imaging photodetector modules 103. Two axes ofadjustment between the registration cap and the imaging photodetectormodules 103 can be provided to allow for imaging of selectable portionsof the brain.

Referring to FIG. 2A, shown is an image of an example of an individualcompact PET imaging photodetector module 103. The imaging photodetectormodule 103 includes a scintillator array 203 with a thickness in therange of 10-25 mm. The scintillator array 203 is coupled through a lightguide 206 to a silicon photomultiplier (SiPM) array 209. A readout board212 interfaces with the SiPM 209 to provide measurement information viaa plurality of readout channels (e.g., 4-32). In one embodiment, amongothers, a PET imaging photodetector module 103 includes Hamamatsumulti-pixel photon counter (MPPC) solid state photodetector technologycoupled to arrays of LYSO pixels with 1.5 mm pitch and 10 mm thick fromProteus. Twelve modules of about 5 cm×5 cm coverage each are arranged ina ring geometry with about 21 cm face-to-face inner diameter. A chargedivision readout from AiT Instruments that employed 4 channels permodule was implemented. The 48 amplified detector signals were digitizedin the FPGA USB2 64ch DAQ module of integrating ADCs developed atJefferson Lab and available from AiT Instruments. A 16-ch MesytecMCFD-16 trigger module produced the coincidence trigger for the DAQmodule between any pair of the 12 ring modules. Read-out software wasimplemented using Java programming language with an overlaying userinterface provided by a Kmax scientific programming package from SparrowCorporation. FIG. 2B is a graph illustrating an example of the overalltiming resolution (380 ps) of a SiPM based PET imaging photodetectormodule 103. As can be seen in FIG. 2B, all subcomponents of the module103 contribute in varying degrees to the overall performance.

FIG. 2C is a cross-sectional view of an example of a module assemblythat can be used to increase the light detection efficiency of the PETimaging photodetector module 103. The module assembly can include twomonolithic slabs of scintillator 203 with dual end readout using SiPMs209. Use of the dual end readout with the use of maximum likelihoodalgorithms can maximize the timing. Simulation results shown in FIG. 2Dshow that a resolution of approximately 1 mm is achievable in thecenter. Closer integration of the electronics and the imagingphotodetector modules 103, and on-chip signal processing algorithms, canimprove the timing and spatial information.

A compact and mobile high resolution brain imaging system can providetomographic slice reconstruction and a 3D reconstruction resolution. Thetight geometry of the imaging photodetector modules 103 about the headof the subject 106 can create response non-uniformity and reconstructionproblems. Special tomographic reconstruction can be used to deal withthe compactness of the geometry and breaks between the individualimaging photodetector modules 103, producing limited angular coveragewith regular (rings) or irregular (set of modules) breaks. A dataacquisition (DAQ) electronics module can be located in a mobilecontainer or cabinet with, e.g., a cable connection between the imagingphotodetector modules 103 and the DAQ module. In some implementations,the DAQ electronics module can wirelessly communicate with the imagingphotodetector modules 103. An on-board computing system can producereconstructed 3D images in a short time after the end of each imagingsession (e.g., a few minutes or less). The brain imaging system canrecord data to enable limited data analysis, fast data replay, and imagereconstruction during the same scan session.

An image reconstruction application, executed by a computing system, canbe used to generate the images from the data from the imagingphotodetector modules 103. Accurate system response matrices can bedetermined for adjustments or variations in the geometric configurationof the imaging photodetector modules 103. The imaging photodetectormodules 103 can be pre-characterized using a single-photon responsefunction (SPRF). The SPRF represents the probability of a photon thatenters the front face of the imaging photodetector module 103 atposition (x,y) with polar and azimuthal angles (φ,θ) being detected bycrystal i of the imaging photodetector module 103. The SPRF can becomputed analytically or determined through simulation using acollimated point source, and stored in memory.

For a pair of imaging photodetector modules 103 in the wearable brainimager 100, the SPRFs can be used to form the coincidence responsefunction for a line projection based on the position and incidence angleof the line projection with respect to each imaging photodetector module103. The computation can be performed very quickly as it can involveonly multiplications of the elements in the SPRFs. In this way, asinogram blurring matrix can be produced that represents the probabilityof a pair of photons emitted along the line projection being detected byany detector pairs. Using the SPRF, the geometric projection matrix andsinogram blurring matrix can be decoupled. The geometric projectionmatrix can be computed on-the-fly using ray-tracing methods. Combinationof the geometric projection matrix and sinogram blurring matrix canprovide an accurate system model for PET image reconstruction.

Factors affecting PET image quality include attenuation, scattered andrandom coincidences, detector efficiency variations, system dead-time,and/or system-wide deadtime. For attenuation correction, TOF-basedcorrection methods can be used. Simulations can be used to evaluate theaccuracy of this approach for the 100-200 ps timing resolutions. Thisapproach may be supplemented with other techniques that start with thenon-attenuation-corrected PET image. Quantitative corrections can alsobe implemented for scatter, randoms, detector efficiency normalizationand deadtime. For scatter, a Bergstrom convolution approach can be useddue to the simple attenuation geometry. A Klein-Nishina based estimationmethod may also be utilized. For randoms, singles based correctionmethods, which are based upon characterization of detector dead-time,can be used. Dead-time can be measured for both distributed and focalsource geometries, and fit to a singles-rate model. Many industrydead-time models are among the most sophisticated available. Forcorrection of detector efficiency variations, a component-basednormalization procedure that decouples detector related factors, such ascrystal efficiencies, block effects, and timing profile, from geometricfactors can be used.

The brain imaging system can provide safe, reliable and comfortableco-registration of the imaging photodetector modules 103 with the headand/or brain of the subject 106, while allowing the subject 106 tofreely move during use. Referring to FIG. 3A, shown are images of asupport system 300 a that allows freedom of movement of the subject 106.In the example of FIG. 3A, the mobile brain imager 100 is suspended froma mobile overhead support frame 303 by a tether 306 (or other flexiblesupport) that extends downward from a support boom 309 of the overheadsupport frame 303. The mobile brain imager 100 can be suspended from arolling support on a spring or counterbalance to enable more flexibleand comfortable placement of the mobile brain imager 100, and can beadjusted vertically on the subject's head to image the desired part ofthe brain. The tether 306 can be secured to the overhead support frame303 at one end and clipped to the mobile brain imager 100 at the otherend, and can be elastic to allow for movement of the subject 106. Thedesign can also permit the mobile brain imager 100 to become detachedfrom the overhead support frame 303. Wired connections from the imagingphotodetector modules 103 to a computing system 312 of the ambulatorybrain imaging system can also be supported by the support boom 309 ofthe overhead support frame 303. While the subject 106 is shown sittingdown in FIG. 3A, the support system 300 a can be adjusted to accommodatemovement while the subject 106 is standing.

FIG. 3B illustrates another example of a support system 300 b thatallows the subject 106 to move freely while wearing the mobile brainimager 100. The self-contained backpack support system 300 b can be wornby the subject 106 is shown in FIG. 3B. A support boom 309 can be usedto transfer the weight of the mobile brain imager 100 to the supportsystem 300 b through a tether or other flexible support, when it isplaced on the head of the subject or patient 106. A gimbal mechanism canbe used to apply a counterbalance force to neutralize the weight of themobile brain imager 100, while allowing for a full six degrees offreedom for the head. A light weight, low friction, and compact gimbalmechanism can minimize distraction of the subject 106. Wired connectionsbetween the imaging photodetector modules 103 and computing system 312can also be supported by the support boom 309. In some embodiments, thecomputing system 312 and power supply can be included in the backpacksupport system 300 b as illustrated in FIG. 3B. Data from the imagingphotodetector modules 103 can be collected and stored by the computingsystem 312, and/or transferred to a local base station via a wirelessconnection. Hardware can manage the cables to avoid risk of electricalshock, excessive fiction and/or entanglement during movement. Anemergency release of the mobile brain imager 100 may also be providedfor safety of the subject 106.

Referring to FIG. 3C, shown is a robotic support system 300 c that moves(“walks” or rides) with the subject and provides a flexiblecounterbalancing support for the weight of the mobile brain imager 100,while minimizing the stress to the subject 106. As in FIG. 3B, a supportboom 309 can be used to transfer the weight of the mobile brain imager100 to the support system 300 c. The support boom 309 can include pivotpoints (or hinges) to allow sections of the boom to swing with themovement of the subject or patient 106 and a gimbal mechanism can beused to neutralize the weight of the mobile brain imager 100, whileallowing for a full six degrees of freedom for the head. Wiredconnections from the imaging photodetector modules 103 to a computingsystem 312 can also be supported by the robotic support system 300 c. Acomputing system 312 and power supply can be supported by the roboticsupport system 300 c as illustrated in FIG. 3C. The computing system 312can also control the movement of the robotic support system 300 c basedupon indications from sensors 315 that monitor the movement of thesubject 106.

When the mobile brain imager 100 is used in conjunction with a virtualreality (VR) system, the impact of stimuli from and/or interactions withthe surrounding environment can be examined. The virtual reality systemcan be configured to simulate a variety of visual, auditory, olfactoryand/or tactile stimuli. A VR control system can be used to control andcoordinate the stimulations provided to the subject or patient 106.Visual stimulation can be implemented using visual interfaces including,but not limited to, video goggles, display screens or other visual meanssuch as mirrors, projection screens, etc. Audio stimulation can beimplemented using headphones, speakers, or other noise generatingdevices. Scent or odor generating devices can be used to provideolfactory stimulation. A variety of sources can be used to providetactile or painful stimulation. For example, jet sprays and/or airnozzles can be used to simulate wet and/or windy conditions. Heat and/orcold can also be simulated by controlling the temperature of the airdirected at the subject 106 or through the use of heating lamps. Hapticor tactile clothing can also be used to provide contact and/or pressuredirectly to the skin of the subject 106. Heating and/or cooling circuitsor devices can also be included in clothing of the subject 106.

As shown in FIG. 4A, subjects 106 wearing a mobile brain imager 100 canalso wear video goggles 403 for visual stimulation during scanningand/or imaging. The goggles 403 can receive video or image inputsthrough a wired or wireless connection with the VR control system.Movement of the subject 106 can be monitored using, e.g., cameras 406,tactile clothing, or other monitoring device that detects the motion ofthe subject 106. The VR control system can monitor the movement andresponse of the subject 106 to the various stimuli, and adjust thestimulation in response. For example, the viewing perspective can beadjusted in response to head or body movement. Similarly, audio and/ortactile stimuli can be adjusted by the VR control system to account forchanges in bodily orientation of the subject 106.

In some implementations, large displays or screens can be used insteadof goggles 403. FIG. 4B shows an example of a virtual reality enclosure409 that surrounds the subject or patient 106 with one or more display.Additional visual, audio, olfactory and/or tactile simulation sourcescan be integrated into the VR enclosure 409. For example, controllablelighting, speakers, air jets, water jets, etc. can be included toenhance the perception of the subject 106. The VR enclosure 409 can alsoinclude cameras and/or other sensors for monitoring the subject'smovement and/or reaction to the stimuli. The VR control system 412 cancontrol the various stimuli in response to the actions and/or reactionsof the subject 106.

A standard treadmill or mobility platform 415 can be used to allow thesubjects or patients to be in motion or in various positions during theimaging. The mobility platform can allow the subject 106 to physicallymove and/or respond to the various stimuli while remaining in the samelocation. For example, the mobility platform 415 can include, e.g., atreadmill to allow the subject 106 to walk and/or run in place, as wellas other safety structures for protection of the subject 106. Themobility platform 415 can also be configured to monitor the positionand/or movement of the subject or patient 106 and provide feedback tothe VR control system 412 and/or the mobile brain imager 100. Referringto FIGS. 5A-5C, shown are images of an example of a mobility platform415 (Virtuix Omni natural motion interface) that includes a concavesurface that enables the subject 106 to walk and/or run with a naturalgait. The position and/or pressure of the subject's feet (or otherportion of the body) on the surface can be detected by the mobilityplatform 415 and communicated to the VR control system 412. A harnesscan be secured to the mobility platform to provide support for thesubject 106.

The effect of a virtual ambulatory environment on the functioning of thebrain can be close to the stimulation experienced by the human brainduring real world situations, while eliminating logistical issues andimproving safety during imaging with the subject 106 in motion. Themobile brain imager 100 offers a low-dose capability that may beattributed to the imaging photodetector modules 103 being placed muchcloser to the patient's head, which increases the geometrical detectionefficiency over that of a standard PET ring in a PET/CT combo. With sizeand efficiency optimization, the mobile brain imager 100 may operate atabout 10% of the standard dose used in PET/CT scans. This dose levelallows multiple PET scans to be performed within a short period of time.Images can be reconstructed using an algorithm that uses 1×1×1millimeter voxels and iterative reconstruction for 10 iterations.Reconstructed images can be displayed using imaging software (e.g.,ImageJ public domain software and/or MIM professional software) tocompare images of the mobile brain imager 100 with PET/CT images.

To achieve high efficiency (and low injection dose), compactness, lowweight, and low cost, the tight geometry of the imaging photodetectormodules 103 surrounding the patient's head is needed, but introduceslarger cracks in angular coverage between the photodetector modules 103.This limits the angular sampling, resulting in increased responsenon-uniformities in the reconstructed images. Correction algorithms canbe used to minimize the effects of the non-uniformities, improving thelevel of image normalization, and enhancing overall image quality.Adding photodetector modules 103 can also reduce the angular geometrycoverage effects.

Testing with the mobile brain imager 100 of FIG. 3A, which includes aring of twelve imaging photodetector modules 103, was carried out.Uniformity correction was performed by image division of thereconstructed 2D slices obtained from an imaged object (e.g., a phantomor a patient's brain) based upon experimentally obtained slice images ofa cylindrical “flood” phantom. The “flood” phantom was a cylindercovering the entire useful field of view of the imager, which was filledwith a F18-FDG water solution with a uniform volume concentration ofradioactivity. The uniformity correction can account for the geometricalresponse matrix of the detectors, as well as for the bulk of the 511 keVannihilation gamma absorption effects. The geometrical response matrixcan include a detector response that accounts for the fact that theimaging photodetector modules 103 have gaps between the modules 103. Inaddition, the detector response can correct for imperfections in theimaging photodetector modules 103 and/or imperfections caused by errorsin the calibration procedure. It was established that both the floodcylinder and the brain are primarily composed of water, and producedvery satisfactory normalization results.

For uniformity calibration and “flood” correction, a 185 mm diameterthin-wall acrylic cylinder was placed inside a ring of PET imagingphotodetector modules 103 and filled with an ¹⁸F water solution ofuniform concentration. Data was then collected (for four hours) toattain high image statistics. Images of phantoms and patients 106 werecollected for much shorter times. Division of the object images by theflood images obtained with the above flood phantom, resulted in uniformand artifact-free corrected images. Prior to imaging patients 106,operation of the mobile brain imager 100 was studied with many differentphantoms of different sizes. The images were reconstructed withabsorption correction and then “normalized” by the system response froma uniform cylinder “flood” phantom.

Four consenting patients 106 were imaged under approved institutionalIRB protocol, following the patient imaging with the whole body mCTPET/CT from Siemens. The patients 106 (all male) were cancer patientsrequiring whole body PET/CT. An additional brain scan is an intrinsicpart of the regular diagnostic patient workout. Imaging with the mobilebrain imager 100 was performed after the PET/CT scans and was dividedinto four components: (1) fast 30 sec scan, (2) 3 min. scan, (3) 10 min.scan, and (4) 1 min. scan with patient intentionally turning his headleft and right by an angle of about +/−45 deg. The last 1 min. scan wasintended to demonstrate that imaging could be performed while thesubject's head was freely moving. Two of the four patients 106 wereimaged immediately following the PET/CT scan, and other two patients 106were imaged after a 4-plus hour waiting period following the whole bodyPET/CT scan.

Referring to FIG. 6, shown is a series of multi-slice reconstructedimages of a multi-compartmental Hoffman brain phantom obtained with themobile brain imager 100. The multi-compartmental Hoffman brain phantomwas filled with uniform volume activity (total activity in the phantomof about 50 microCurie). The series includes twelve reconstructed 1 mmslices through the brain phantom. The images show that an object of thesize of a human brain can be imaged with the mobile brain imager 100,with good spatial resolution (about 2.5 mm FWHM). The images of FIG. 6demonstrate good uniformity of imaging in the whole phantom, despite thetight imaging geometry of the imaging photodetector modules 103.

With respect to the patient images, the imaging sessions for the firstpair of patients 106 suffered from the high rate problems manifestingthemselves in rate-induced DC shifts in the signal outputs of theimaging photodetector modules 103 and ultimately resulting in imagedistortions and artifacts that were not software correctable. The dataacquisition system was capable of accepting all incoming event rates,but the rate issue was in the solid-state SiPM sensors and theassociated electronics. The second pair of patients 106 was imaged 4+hours after imaging with the PET/CT. The obtained images were ofsufficient quality to analyze and compare with the PET/CT images of thepatient's head and the selected results are presented here in FIGS.7A-9B.

FIG. 7A shows human brain images acquired in a 600 sec scan of a patient106 using the mobile brain imager 100. The images illustrate PET slicesin 4 mm increments, with a 4 mm FWHM resolution. FIG. 7B shows clinicalpatent images of 8 mm slices filtered with equivalent 8 mm FWHMresolution.

FIG. 8A shows representations of PET/CT images (top row) and mobilebrain imager 100 images (middle row) from a patient 106. Though theimages from the mobile brain imager 100 have poorer quality (primarilydue to limited image processing), the structures observed in the mobilebrain imager 100 images correlate well with the PET/CT images (as can beseen from the overlaid images in the bottom row). The images from themobile brain imager 100 are missing some front and back edge parts ofthe head due to the tight placement of the imaging photodetector modules103 on the patient's head. In addition, some differences may beattributed to obtaining the images with the mobile brain imager 100 morethan 4 hours after the PET/CT scan. FIG. 8B shows CT images alone (toprow), mobile brain imager 100 images (middle row), and overlaid images(bottom row) from the same patient of FIG. 8A, but with a differentreconstruction slice.

Referring now to FIG. 9A, shown are images of four central 4 mm slicesthat were obtained from a patient 106 with a 60 sec scan using themobile brain imager 100 while the patient 106 was turning his head leftand right by about +/−45 deg. The images demonstrate that the mainF18-FDG uptake features remain stable despite a substantial headmovement during the scan. The effective post-filtering resolution is 8mm FWHM. FIG. 9B shows six 8 mm slices obtained from a second patient106 with a 60 sec scan using the mobile brain imager 100 while thepatient 106 was turning his head left and right by about +/−45 deg. Inthis case, the mobile brain imager 100 was placed higher on thepatient's head, resulting in images of the top of the patient's head(left top). The effective post-filtering resolution is again 8 mm FWHM.

A wearable mobile brain imager 100 has been demonstrated by the humanbrain PET scans obtained using the device. Mounting the mobile brainimager 100 on the head of the patient 106 was possible with propermechanical support. The results demonstrate the feasibility of atwo-three ring mobile brain imager 100, which could operate with areduced injected dose of a radiolabeled compound. Scan times as short as60 seconds or 30 seconds obtained images that show the key features ofthe distribution pattern of the F18-FDG uptake. Taking into account thatthe images were taken 4 hours-plus after injection, and that thestandard PET/CT images were obtained in 300 seconds, it may be feasibleto lower the injected dose by a factor 10 or more for uptake patternimaging.

The mobile brain imager 100 cam be beneficial in the investigation ofrecovery from stroke, as well as other brain conditions that impactfunctionality of the brain in upright (sitting or standing) position. Inaddition, while dementia patients do not need upright imaging, theyoften have problems maintaining steady head position during PET scans oftheir brain. The wearable and naturally co-registered (and low-dose) PETimager can be a good option for these patients.

Mobile brain imagers 100 with additional rows or hemispherical coveragecan provide more brain coverage and increased detection efficiency.Increasing the ring diameter to 24-25 cm from the current 21 cm can alsoavoid cutting the periphery of the objects in the reconstructed images,as observed in FIG. 8A. The LYSO scintillator may also be replaced byBGO in some embodiments, or a TOFPET option with LYSO or similar fastscintillator may be implemented. Patient comfort should also beconsidered with all designs.

It should be emphasized that the above-described embodiments of thepresent disclosure are merely possible examples of implementations setforth for a clear understanding of the principles of the disclosure.Many variations and modifications may be made to the above-describedembodiment(s) without departing substantially from the spirit andprinciples of the disclosure. All such modifications and variations areintended to be included herein within the scope of this disclosure andprotected by the following claims.

It should be noted that ratios, concentrations, amounts, and othernumerical data may be expressed herein in a range format. It is to beunderstood that such a range format is used for convenience and brevity,and thus, should be interpreted in a flexible manner to include not onlythe numerical values explicitly recited as the limits of the range, butalso to include all the individual numerical values or sub-rangesencompassed within that range as if each numerical value and sub-rangeis explicitly recited. To illustrate, a concentration range of “about0.1% to about 5%” should be interpreted to include not only theexplicitly recited concentration of about 0.1 wt % to about 5 wt %, butalso include individual concentrations (e.g., 1%, 2%, 3%, and 4%) andthe sub-ranges (e.g., 0.5%, 1.1%, 2.2%, 3.3%, and 4.4%) within theindicated range. The term “about” can include traditional roundingaccording to significant figures of numerical values. In addition, thephrase “about ‘x’ to ‘y’” includes “about ‘x’ to about ‘y’”.

Therefore, at least the following is claimed:
 1. A system for virtualambulatory environment brain imaging, comprising: a mobile brain imagerconfigured to obtain positron emission tomography (PET) scans of asubject in motion; and a virtual reality (VR) system configured toprovide one or more stimuli to the subject during the PET scans.
 2. Thesystem of claim 1, wherein the mobile brain imager comprises an array ofimaging photodetector modules distributed in a hemisphere about a headof the subject.
 3. The system of claim 1, wherein the mobile brainimager comprises an array of imaging photodetector modules distributedin a cylinder about a head of the subject.
 4. The system of claim 3,wherein the array of imaging photodetector modules extend over the eyesof the subject.
 5. The system of claim 1, wherein the mobile brainimager comprises compact goggles configured to provide visualstimulation to the subject, the compact goggles positioned between thephotodetector modules and the eyes of the subject.
 6. The system ofclaim 1, further comprising a support system configured to provide acounterbalance force to neutralize a weight of the mobile brain imager.7. The system of claim 6, wherein the support system allows a head ofthe subject to move with six degrees of freedom when wearing the mobilebrain imager.
 8. The system of claim 6, wherein the support system is aself-contained backpack support system.
 9. The system of claim 6,wherein the support system is a robotic support system.
 10. The systemof claim 1, wherein the VR system comprises a VR control systemconfigured to control at least one virtual interface configured tostimulate the subject.
 11. The system of claim 10, wherein the at leastone virtual interface comprises a visual interface.
 12. The system ofclaim 11, wherein the at least one virtual interface further comprises atactile interface.
 13. The system of claim 10, wherein the VR controlsystem controls the at least one virtual interface in response tomovement of the subject.
 14. The system of claim 10, wherein the VRsystem comprises a mobility platform in communication with the VRcontrol system, the mobility platform configured to monitor movement ofthe subject.
 15. A method for virtual ambulatory environment brainimaging, comprising: providing stimulation to a subject through avirtual reality (VR) system; and obtaining a positron emissiontomography (PET) scan of a brain of the subject while the subject ismoving in response to the stimulation from the VR system.
 16. The methodof claim 15, comprising positioning a mobile brain imager on thesubject, the mobile brain imager comprising an array of imagingphotodetector modules distributed about the head of the subject toobtain the PET scan.
 17. The method of claim 16, wherein the mobilebrain imager comprises compact goggles configured to provide visualstimulation to the subject, the compact goggles positioned between thephotodetector modules and the eyes of the subject.
 18. The method ofclaim 16, wherein a support system provides a counterbalance force toneutralize a weight of the mobile brain imager.
 19. The method of claim15, wherein a VR control system controls the stimulation provided to thesubject in response to movement of the subject.
 20. The method of claim19, wherein the stimulation provided to the subject comprises tactilestimulation.